Lonely in Depression

Montgomery-Åsberg Depression Rating Scale (MADRS) (10 Items, each item rated 0-6 points, minimum 0 points, maximum 60 points, higher scores indicate greater severity of depressive symptoms)

3 Item UCLA Loneliness Scale (3-Item UCLA) (3 items, each item rated 1-3 points, minimum 3 points, maximum 9 points, higher scores indicate greater loneliness)

Patient Health Questionnaire, 9-Item Depression Scale (PHQ-9) (9 Items, each item rated 0-4 points, minimum 0 points, maximum 27 points, higher scores indicate greater severity of depression)

6-Item short scales for Loneliness, De Jong Gierveld Loneliness Scale (6-Item DJGLS) (6 Items, each item rated 1-3 points, before the total score is calculated, the items are dichotomized, thus resulting in a sum score ranging from 0 to 6, wherein scores of 0-1 indicate no loneliness, 2-4 indicate moderate loneliness, and 5-6 indicate severe loneliness)

Fragebogen zur Sozialen Unterstützung (F-SoZ-U 14) (14 Item shortend form, each item rated 0-4 points, minimum 0 points, maximum 56 points, higher total scores indicating higher levels of perceived social support)

in days

World Health Organization-Five Well-Being Index (WHO-5) (5 Items, each item rated 0-5 points, minimum 0 points, maximum 25 points, the total score (0-25) is transformed to a scale ranging from 0 to 100, with scores ≤50 indicating diminished well-being and higher scores representing higher well-beeing)

As there is no culture and language adapted version of a social network indice available an adapted and German-translated version is used to capture participants' social interaction partners during the prior two weeks. The questionnaire was newly developed, with item content informed by existing validated scales (Cohen Social Network Index (SNI), Lubben Social Network Scale (LSNS), Berkman - Social Network/Integration).

Via the use of a yes/no response format, participants indicated whether they had personal or telephone contact with each of the following: (1) spouse or partner, (2) own children, (3) parents or parent-like figures, (4) other relatives (e.g., siblings, uncles, or aunts), (5) friends, (6) neighbors, (7) colleagues, (8) people known through voluntary activities, (9) in-laws (parents, sons, or daughters-in-law), and (10) members of their social group (e.g., community, congregation, sports, or music clubs).

Higher total scores indicate greater social connectedness.

Short Form 12 Health Survey (SF-12) (12 Items, Items rated 0-1, 1-3 and 1-5 and 1-6 scores represent eight dimensions of physical and mental well-beeing with two composite scores, items are recodet, z-transformed and normed, higher values indicate better health)

Social Phobia Inventory (SPIN) (17 Items, each item rated 0-4 points, minimum 0 points, maximum 68 points, higher scores indicate greater severity of social anxiety, three subscales are available (fear 6 items, avoidance 7 items, physiological distress 4 items))

13-Item Somatic Symptom Severity Scale of the Patient Health Questionnaire (PHQ-13) (13 Items, each item rated 0-2 points, minimum 0 points, maximum 34 points, higher values indicating more somatic symptoms)

LDL cholesterin [mg/dl or mmol/l], higher values (> 100 mg/dl or > 2.6 mmol/l) represent unfavorable metabolic risk

HDL cholesterin [mg/dl or mmol/l), < 40 mg/dl men and < 50 mg/dl women represents unfavorable metabolic risk, ≥ 40 mg/dl men ≥ 50 mg/dl women acceptable, ≥ 60 mg/dl protective

HbA1c [%], higher values (> 5.7%) represent unfavorable metabolic risk

Sphingolipid metabolism enzyme activity of secretory acid sphingomyelinase (S-ASM) [nmol/mL/h/µL], higher leveles represent more inflammation/apoptosis enzyme activity of neutral acid sphingomyelinase (N-ASM) [nmol/mL/h/µL], higher levels represent cellular stress/apotosis Ceramide [nmol/L], higher levels represent more inflammation/apoptosis

brain-derived neurotrophic factor [ng/mL], higher levels represent more neuroplasticity

Cortisol [µg/dL or nmol/L] and timepoint of blood test higher levels represent more stress response

C-reactive protein (CRP) [mg/L], higher levels show systemic inflammation

saliva cortisol (awakening and before bedtime), higher levels represent more stress response

saliva α-amylase activity [U/ml] (awakening and before bedtime), higher levels represent more stress response

alpha-diversity

measures in clinical interview (Montgomery-Åsberg Depression Rating Scale (MADRS)) (Item No. 10 out of 10 items, rated 0-6, higher values represent more suicidality)

9-Item Patient Health Questionnaire (PHQ-9) (Item No. 9 out of 9, rated 0-3 with higher scores indicating more suicidality)

≥ 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score from T0 to T1 (10 Items, each item rated 0-6 points, minimum 0 points, maximum 60 points, higher scores indicate greater severity of depressive symptoms)

≥ 10 points more from T1 to T2 in Montgomery-Åsberg Depression Rating Scale (MADRS) score or ≥ 22 points at T2 (10 Items, each item rated 0-6 points, minimum 0 points, maximum 60 points, higher scores indicate greater severity of depressive symptoms)

consideration of these classes of antidepressant drugs if these are given in a dosage that is effective as an antidepressant (e.g. for Mirtazapin not 7.5 mg, starting from 15 mg): SSRI/SNRI/NaSSA(Mirtazapin)/NDRI (Buproprion)/TZA/MAO-I/SARI (Trazodon)Agomelatin/other with classes of augmentation strategy: Lithium/antipsychotics/second antidepressant/other augmentation strategy sorted as: antidepressant monotherapy/antidepressant augmented therapy/other and change in therapy stategy (1. no; 2. yes drug substance (2.1) added/ (2.2) changed/ (2.3) removed; 3. yes dosage of antidepressant changed (3.1) increased/(3.2) decreased; 4. augmentation strategy changed)

Given the absence of an established measure capable of differentiating between enduring (trait) and situational (state) loneliness, this aspect is captured by using a newly developed single item: 'In looking back upon my life, I would say that I have felt …'. Participants respond to this item on a four-point scale (1= mostly lonely throughout my life, 2= lonely from time to time, 3= only lonely at present, and 4= never lonely). Responses of 1 are intended to represent trait loneliness; options 2 and 3 represent state loneliness; and option 4 indicates no loneliness.

frequency per week of psychotherapy, group interventions and other